scholarly journals Over-Expression of βII-Tubulin and Especially Its Localization in Cell Nuclei Correlates with Poorer Outcomes in Colorectal Cancer

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 25 ◽  
Author(s):  
Kseniya Ruksha ◽  
Artur Mezheyeuski ◽  
Alexander Nerovnya ◽  
Tatyana Bich ◽  
Gennady Tur ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibody ◽  
Cancer Progression ◽  
Nuclear Localization ◽  
Cancer Growth ◽  
Transformed Cells ◽  
Regulatory Pathway ◽  
Cell Nuclei ◽  
Normal Cells ◽  
Over Expression

Tubulin is a heterodimer of α and β subunits, both existing as isotypes differing in amino acid sequence encoded by different genes. Specific isotypes of tubulin have associations with cancer that are not well understood. Previous studies found that βII-tubulin is expressed in a number of transformed cells and that this isotype is found in cell nuclei in non-microtubule form. The association of βII expression and its nuclear localization with cancer progression has not previously been addressed. We here used a monoclonal antibody to βII to examine patients with colorectal cancer and found that patients whose tumors over-express βII have a greatly decreased life expectancy which is even shorter in those patients with nuclear βII. Our results suggest that βII-tubulin may facilitate cancer growth and metastasis and, to accomplish this, may not need to be in microtubule form. Furthermore, βII expression and localization could be a useful prognostic marker. We also found that βII appears in the nuclei of otherwise normal cells adjacent to the tumor. It is possible therefore that cancer cells expressing βII influence nearby cells to do the same and to localize βII in their nuclei by an as yet uncharacterized regulatory pathway.

scholarly journals Alterations in Cell-Extracellular Matrix Interactions during Progression of Cancers

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Rajeswari Jinka ◽  
Renu Kapoor ◽  
Pavana Goury Sistla ◽  
T. Avinash Raj ◽  
Gopal Pande
Keyword(s):  
Extracellular Matrix ◽  
Cancer Progression ◽  
Cell Transformation ◽  
Tumor Model ◽  
Genetic Alterations ◽  
Model Systems ◽  
Transformed Cells ◽  
Normal Cells ◽  
Multistep Process ◽  
Extracellular Matrix Interactions

Cancer progression is a multistep process during which normal cells exhibit molecular changes that culminate into the highly malignant and metastatic phenotype, observed in cancerous tissues. The initiation of cell transformation is generally associated with genetic alterations in normal cells that lead to the loss of intercellular- and/or extracellular-matrix- (ECM-) mediated cell adhesion. Transformed cells undergo rapid multiplication and generate more modifications in adhesion and motility-related molecules which allow them to escape from the original site and acquire invasive characteristics. Integrins, which are multifunctional adhesion receptors, and are present, on normal as well as transformed cells, assist the cells undergoing tumor progression in creating the appropriate environment for their survival, growth, and invasion. In this paper, we have briefly discussed the role of ECM proteins and integrins during cancer progression and described some unique conditions where adhesion-related changes could induce genetic mutations in anchorage-independent tumor model systems.

scholarly journals Abnormal level of paxillin in cervical cancer cells is involved in tumor progression and invasion

2021 ◽  
Author(s):  
Hongqing Gu ◽  
Jing Wen
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Uterine Cervical Cancer ◽  
Cancer Growth ◽  
Over Expression ◽  
Apoptosis Inhibition ◽  
Cervical Cancer Cells ◽  
Elevated Expression ◽  
Abnormal Level

Human papillomavirus (HPV) is the primary causative agent for the uterine cervical cancer. The expression of oncoproteins E6/E7 promotes apoptosis inhibition and increases the risk of cervical cancer progression. Some research reported that elevated expression of paxillin (PXN) stimulated cancer growth and invasion. However, the clinical significance of PXN in cervical cancer has not been well characterized so far. We found that PXN mRNA expression and protein level are significantly upregulated in cervical cancer cells compared to adjacent normal cells. Furthermore, the paxillin over-expression was correlated with potential of tumorigenesis and invasion. Cervical cancer cells with increased paxillin expression had an ability to form more tumor clones and were characterized by higher invasiveness as well. Therefore, our findings suggest that paxillin may act as an important prognostic factor for cervical cancer patients as it promotes tumor regeneration and invasion.

scholarly journals Regulation Network of Colorectal Cancer Specific Enhancers in Progression of Colorectal Cancer

2021 ◽  
Author(s):  
Bohan Chen ◽  
Yiping Ma ◽  
Jinfang Bi ◽  
Wenbin Wang ◽  
Anshun He ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Chromatin Structure ◽  
Therapeutic Targets ◽  
Higher Order ◽  
Epigenetic Changes ◽  
Rna Seq ◽  
Normal Cells ◽  
Regulation Network

Enhancers regulate multiple genes through higher-order chromatin structure and further affect cancer progression. Epigenetic changes in cancer cells activate several cancer specific enhancers that are silenced in normal cells. These cancer specific enhancers are potential therapeutic targets of cancer. However, functions and regulation network of colorectal cancer specific enhancers are still unknown. Here in this study, we profile colorectal cancer specific enhancers and reveal the regulation network of these enhancers by analysis of HiChIP, Hi-C and RNA-seq data. We propose the regulation network of colorectal cancer specific enhancers plays important role in progression of colorectal cancer.

scholarly journals Cytotoxic cationic peptides as а ligands for receptor nucleolin

2018 ◽  
Vol 5 (3) ◽  
pp. 59-64
Author(s):  
A. A. Lushnikova ◽  
A. V. Kostarev ◽  
D. A. Ponkratova ◽  
A. V. Onyan ◽  
E. G. Glubokova ◽  
...  
Keyword(s):  
High Frequency ◽  
Peptide Ligands ◽  
Cationic Peptides ◽  
Cell Nuclei ◽  
Tumor Cell Death ◽  
Active Centre ◽  
Normal Cells ◽  
Over Expression ◽  
Cell Functions ◽  
Energy Stable

Background. Chaperone proteins nucleolin (NCL, or C23) and nucleophosmin (NPM, or B23) regulate key cell functions. The most tumors are characterized by over-expression of these proteins, especially in cell nuclei and on the сell surface, as NCL. Differential expression of NCL/NPM in tumor and normal cells is the basis of selective cytotoxicity of cationic peptides – expected ligands for these proteins. Objective. Analysis of the interactions between nucleolin and some peptides with high nonspecific toxicity for tumor cells. Materials and methods. The interaction of 4 previously characterized cationic peptides with nucleolin dimer was analyzed by pair molecular docking using Maestro 11 program. Results and conclusion. It is shown that these peptides can associate with receptor nucleolin molecules, forming energy-stable complexes. In the active centre of NCL molecule were found, at least, 7 positions of amino acids, which bind to the tested peptides at a high frequency (43–100 %). This indicates the conservative structure of dimer NCL, its stable binding to peptide ligands and the possibility of design the optimal structure of cationic peptides that induce tumor cell death due to competing binding to the target proteins.

Computational Analysis of miRNA and their Gene Targets Significantly Involved in Colorectal Cancer Progression

MicroRNA ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 68-75 ◽  
Author(s):  
Jeyalakshmi Kandhavelu ◽  
Kumar Subramanian ◽  
Amber Khan ◽  
Aadilah Omar ◽  
Paul Ruff ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Progression ◽  
Target Prediction ◽  
Computational Prediction ◽  
Initial Step ◽  
Kegg Pathways ◽  
Candidate Mirnas ◽  
Common Cancer ◽  
Colon Cancer Progression

Background:Globally, colorectal cancer (CRC) is the third most common cancer in women and the fourth most common cancer in men. Dysregulation of small non-coding miRNAs have been correlated with colon cancer progression. Since there are increasing reports of candidate miRNAs as potential biomarkers for CRC, this makes it important to explore common miRNA biomarkers for colon cancer. As computational prediction of miRNA targets is a critical initial step in identifying miRNA: mRNA target interactions for validation, we aim here to construct a potential miRNA network and its gene targets for colon cancer from previously reported candidate miRNAs, inclusive of 10 up- and 9 down-regulated miRNAs from tissues; and 10 circulatory miRNAs. </P><P> Methods: The gene targets were predicted using DIANA-microT-CDS and TarBaseV7.0 databases. Each miRNA and its targets were analyzed further for colon cancer hotspot genes, whereupon DAVID analysis and mirPath were used for KEGG pathway analysis.Results:We have predicted 874 and 157 gene targets for tissue and serum specific miRNA candidates, respectively. The enrichment of miRNA revealed that particularly hsa-miR-424-5p, hsa-miR-96-5p, hsa-miR-1290, hsa-miR-224, hsa-miR-133a and has-miR-363-3p present possible targets for colon cancer hallmark genes, including BRAF, KRAS, EGFR, APC, amongst others. DAVID analysis of miRNA and associated gene targets revealed the KEGG pathways most related to cancer and colon cancer. Similar results were observed in mirPath analysis. A new insight gained in the colon cancer network pathway was the association of hsa-mir-133a and hsa-mir-96-5p with the PI3K-AKT signaling pathway. In the present study, target prediction shows that while hsa-mir-424-5p has an association with mostly 10 colon cancer hallmark genes, only their associations with MAP2 and CCND1 have been experimentally validated.These miRNAs and their targets require further evaluation for a better understanding of their associations, ultimately with the potential to develop novel therapeutic targets.

scholarly journals Carbohydrate-conjugated 4-(1,3,2-dithiarsolan-2-yl)aniline as a cytotoxic agent against colorectal cancer

RSC Advances ◽  
2018 ◽  
Vol 8 (71) ◽  
pp. 40760-40764
Author(s):  
Boqiao Fu ◽  
Xiaolin Wang ◽  
Yingjie Li ◽  
Jingying Hu ◽  
Dai Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Index ◽  
Chemotherapeutic Agents ◽  
Cytotoxic Agent ◽  
Normal Cells

We synthesized a carbohydrate-conjugated 4-(1,3,2-dithiarsolan-2-yl)aniline. It exhibited reduced cytotoxicity to normal cells, suggesting a feasible approach to improve the therapeutic index of arsenic-containing compounds as chemotherapeutic agents.

scholarly journals RNF141 interacts with KRAS to promote colorectal cancer progression

Oncogene ◽  
2021 ◽  
Author(s):  
Jiuna Zhang ◽  
Xiaoyu Jiang ◽  
Jie Yin ◽  
Shiying Dou ◽  
Xiaoli Xie ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Plasma Membrane ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Critical Role ◽  
Ring Finger ◽  
Immunohistochemical Analysis ◽  
Bimolecular Fluorescence Complementation

AbstractRING finger proteins (RNFs) play a critical role in cancer initiation and progression. RNF141 is a member of RNFs family; however, its clinical significance, roles, and mechanism in colorectal cancer (CRC) remain poorly understood. Here, we examined the expression of RNF141 in 64 pairs of CRC and adjacent normal tissues by real-time PCR, Western blot, and immunohistochemical analysis. We found that there was more expression of RNF141 in CRC tissue compared with its adjacent normal tissue and high RNF141 expression associated with T stage. In vivo and in vitro functional experiments were conducted and revealed the oncogenic role of RNF141 in CRC. RNF141 knockdown suppressed proliferation, arrested the cell cycle in the G1 phase, inhibited migration, invasion and HUVEC tube formation but promoted apoptosis, whereas RNF141 overexpression exerted the opposite effects in CRC cells. The subcutaneous xenograft models showed that RNF141 knockdown reduced tumor growth, but its overexpression promoted tumor growth. Mechanistically, liquid chromatography-tandem mass spectrometry indicated RNF141 interacted with KRAS, which was confirmed by Co-immunoprecipitation, Immunofluorescence assay. Further analysis with bimolecular fluorescence complementation (BiFC) and Glutathione-S-transferase (GST) pull-down assays showed that RNF141 could directly bind to KRAS. Importantly, the upregulation of RNF141 increased GTP-bound KRAS, but its knockdown resulted in a reduction accordingly. Next, we demonstrated that RNF141 induced KRAS activation via increasing its enrichment on the plasma membrane not altering total KRAS expression, which was facilitated by the interaction with LYPLA1. Moreover, KRAS silencing partially abolished the effect of RNF141 on cell proliferation and apoptosis. In addition, our findings presented that RNF141 functioned as an oncogene by upregulating KRAS activity in a manner of promoting KRAS enrichment on the plasma membrane in CRC.

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